t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth

Ansell, Stephen M.; Akasaka, Takashi; McPhail, Ellen D.; Manske, Michelle K.; Braggio, Esteban; Price-Troska, Tammy; Ziesmer, Steven C.; Secreto, Frank J.; Fonseca, Rafaël; Gupta, Mamta; Law, Mark E.; Witzig, Thomas E.; Dyer, Martin J. S.; Doğan, Ahmet; Cerhan, James R.; Novak, Anne J.

doi:10.1182/blood-2011-11-389908

Cited by 52 publications

(40 citation statements)

References 39 publications

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“…GPR34 belongs to the P2Y 12 -like receptor group, and its expression levels have been related to impaired immunity (6,11) and development of lymphoma and gastric cancer (35)(36)(37)(38). Upregulation of the receptor has also been linked to neuroinflammation (9).…”

Section: Discussionmentioning

confidence: 99%

Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Jäger

Schulz

Lede

et al. 2016

The Journal of Immunology

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Dendritic cells (DCs) are specifically equipped with the G protein–coupled receptor 34 (GPR34). Tight regulation of GPR34 gene expression seems highly important for proper immunological functions, because the absence of this receptor leads to an alteration of the immune response, whereas overexpression was reported to be involved in neuroinflammation. However, the regulatory mechanism of GPR34 expression has not yet been investigated. Whole-transcriptome RNA sequencing analysis from spleens and DCs of GPR34 knockout and wild-type mice, combined with protein–protein interaction data, revealed functional modules affected by the absence of this receptor. Among these, NF-κB, MAPK, and apoptosis-signaling pathways showed high significance. Using murine DCs we experimentally show that NF-κB and MAPK pathways are involved in the downregulation of GPR34. DCs lacking GPR34 have a higher caspase-3/7 activity and increased apoptosis levels. Our study reveals a novel role of GPR34 in the fate of DCs and identifies a regulatory mechanism that could be relevant for treatment of GPR34-overexpressing pathologies, such as neuroinflammatory or cancer conditions.

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Section: Discussionmentioning

confidence: 99%

Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Jäger

Schulz

Lede

et al. 2016

The Journal of Immunology

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“…When compared to healthy B and T cells, GPR34 mRNA expression was significantly upregulated in MALT, nodal and splenic MZL and increased gene expression of GPR34 in was correlated with high expression of the orphan receptor GPR82. Overexpression of GPR34 in cell culture experiments resulted in increased cell proliferation and increased phosphorylation of the kinases ERK and PKC and cAMP response element-binding protein (CREB) [185]. …”

Section: Marginal Zone Lymphomamentioning

confidence: 99%

The role of G protein-coupled receptors in lymphoid malignancies

Nugent

Proia

2017

Cellular Signalling

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B cell lymphoma consists of multiple individual diseases arising throughout the lifespan of B cell development. From pro-B cells in the bone marrow, through circulating mature memory B cells, each stage of B cell development is prone to oncogenic mutation and transformation, which can lead to a corresponding lymphoma. Therapies designed against individual types of lymphoma often target features that differ between malignant cells and the corresponding normal cells from which they arise. These genetic changes between tumor and normal cells can include oncogene activation, tumor suppressor gene repression and modified cell surface receptor expression. G protein-coupled receptors (GPCRs) are an important class of cell surface receptors that represent an ideal target for lymphoma therapeutics. GPCRs bind a wide range of ligands to relay extracellular signals through G protein-mediated signaling cascades. Each lymphoma subgroup expresses a unique pattern of GPCRs and efforts are underway to fully characterize these patterns at the genetic level. Aberrations such as overexpression, deletion and mutation of GPCRs have been characterized as having causative roles in lymphoma and such studies describing GPCRs in B cell lymphomas are summarized here.

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“…By using interphase fluorescence in situ hybridization (FISH), Ansell and his colleagues found a novel translocation involving the IGH locus and an unknown partner in a primary MALT lymphoma patient with SS [67]. This unknown partner is now confirmed to be the X chromosome, resulting in the deregulation of the expression of the G-protein-coupled receptor, GPR34.…”

Section: T(x;14)(p11;q32)-igh-gpr34mentioning

confidence: 99%

“…Increased levels of GPR34 were detected in MZL tumor cells and normal immune cells. The overexpression of GPR34 results in the phosphorylation of extracellular signal regulated kinase (ERK) and protein kinase C (PKC) and induces NF-B-related gene transcription, thus leading to increased cell proliferation [67].…”

Section: T(x;14)(p11;q32)-igh-gpr34mentioning

confidence: 99%

Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue—from (auto)antigen driven selection to the activation of NF-κB signaling

Zhang

Wei

et al. 2015

Sci. China Life Sci.

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Lymphomas of mucosa-associated lymphoid tissue (MALT) are typically present at sites such as the stomach, lung or urinary tract, where lymphoid tissues scatter in mucosa lamina propria, intra-or sub-epithelial cells. The infection of certain pathogens, such as Helicobacter pylori, Chlamydophila psittaci, Borrelia burgdorferi, hepatitis C virus, or certain autoantigens cause these sites to generate a germinal center called the "acquired lymphoid tissue". The molecular pathogenesis of MALT lymphoma is a multi-step process. Receptor signaling, such as the contact stimulation of B cell receptors and CD4 positive T cells mediated by CD40/CD40-ligand and T helper cell type 2 cytokines like interleukin-4, contributes to tumor cell proliferation. A number of genetic alterations have been identified in MALT lymphoma, and among them are important translocations, such as t(11;18)(q21;q21), t(1;14)(p22;q32), t(14;18)(q32;q21) and t(3;14)(p13;q32). Fusion proteins generated by these translocations share the same NF-B signaling pathway, which is activated by the caspase activation and recruitment domain containing molecules of the membrane associated guanylate kinase family, B cell lymphoma-10 and MALT1 (CBM) protein complex. They act downstream of cell surface receptors, such as B cell receptors, T cell receptors, B cell activating factors and Toll-like receptors, and participate in the biological process of MALT lymphoma. The discovery of therapeutic drugs that exclusively inhibit the antigen receptor signaling pathway will be beneficial for the treatment of B cell lymphomas in the future. malt lymphoma, helicobacter pylori, chromosomal translocation, genetic alteration, NF-B Citation:Zhang YA, Wei Z, Li J, Liu P. Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue-from (auto)antigen driven selection to the activation of NF-B signaling.

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t(X;14)(p11;q32) in MALT lymphoma involving GPR34 reveals a role for GPR34 in tumor cell growth

Cited by 52 publications

References 39 publications

Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

Dendritic Cells Regulate GPR34 through Mitogenic Signals and Undergo Apoptosis in Its Absence

The role of G protein-coupled receptors in lymphoid malignancies

Molecular pathogenesis of lymphomas of mucosa-associated lymphoid tissue—from (auto)antigen driven selection to the activation of NF-κB signaling

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